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Lithium

Last updated: January 20, 2021

Summary

Lithium is a psychiatric medication used primarily as a first-line therapy for bipolar disorder. It is also used in treatment-resistant depression to augment antidepressants. The specific mechanism by which lithium acts to stabilize mood is not definitively known, but it is thought to be due to inhibition of the phosphoinositol cascade. Common side effects include gastrointestinal distress (nausea, diarrhea), polyuria, polydipsia, and tremor. Lithium therapy has a very narrow therapeutic index; frequent monitoring is therefore required to prevent toxicity.

Pharmacodynamics

  • Mechanism of action: While the mechanism of action has not been definitively established, inhibition of the phosphoinositol cascade is thought to result in mood stabilization.
  • Steady state: usually reached 4–5 days after initiation or a change in dosage

Pharmacokinetics

Indications

Adverse effects

General adverse effects [2]

Adverse effects occur at therapeutic levels (0.4–1.0 mEq/L) but tend to be more severe at peak serum concentration of the drug.

Nonspecific

Motor

  • Fine tremor
    • Nonprogessive, symmetric, fine postural tremor in the distal ends of upper extremities
    • Typically occurs when lithium therapy is started or the dose is increased but can occur at any time during the course of treatment
    • Often decreases spontaneously over time
  • Muscle weakness

Dermal

Cardiac [3]

Thyroid

Renal

Teratogenicity

Lithium toxicity [4]

Toxicity occurs at serum levels > 1.5 mEq/L.

Causes

Clinical features

LITHIUM: “Lithium can cause Irregular Thyroxine levels (hypothyroidism or hyperthyroidism), Heart (Ebstein anomaly), nephrogenic diabetes Insipidus, and Uncontrolled Muscle movements (tremor).”

Treatment of adverse effects [5][6]

  • General measures
    • Reassurance, avoidance of exacerbating factors (e.g., caffeine, stress), and follow-up
    • Dosage adjustment
      • Use of short-acting lithium preparations, divided doses, or a different lithium salt (e.g., citrate instead of carbonate)
      • Reducing the total daily dose of lithium if serum lithium concentration is close to the upper limit of the therapeutic range
  • Tremor: beta blockers (e.g., propranolol) if persistent or severe tremor
  • Nephrogenic diabetes insipidus: amiloride [7]
  • Lithium toxicity
    • Discontinuation of lithium
    • Hydration with isotonic fluid (0.9% NaCl solution) and electrolyte correction to promote lithium clearance
    • Hemodialysis: first-line treatment for severe lithium toxicity
      • Indications
        • Serum lithium concentration > 5.0 mEq/L
        • Serum lithium concentration > 4.0 mEq/L with kidney dysfunction
        • Altered mental status, seizures, and/or life-threatening arrhythmias
      • Hemodialysis should be continued until serum lithium concentration is < 1.0 mEq/L or for a minimum of 6 hours (if the serum lithium concentration cannot be measured).
    • Ventilatory support if required
    • Whole bowel irrigation with polyethylene glycol can also be considered.
    • Activated charcoal does not prevent the absorption of lithium.

Monitoring serum levels of lithium is important because of its narrow therapeutic window.

We list the most important adverse effects. The selection is not exhaustive.

Contraindications

Alternative maintenance treatment options for bipolar disorder include lamotrigine, valproate, and carbamazepine. Valproate and antipsychotics (e.g., olanzepine, quetiapine) can be used for treatment of acute mania and hypomania.

Before prescribing lithium to women of child-bearing age, evaluate thyroid function, renal function, and human chorionic gonadotropin levels to rule out pregnancy.

We list the most important contraindications. The selection is not exhaustive.

References

  1. Willem A Nolen. What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disorders. 2019 .
  2. Mehta N, Vannozzi R. Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017; 40 (12): p.1363-1367. doi: 10.1002/clc.22822 . | Open in Read by QxMD
  3. Timmer RT, Sands JM. Lithium intoxication.. J Am Soc Nephrol. 1999; 10 (3): p.666-74.
  4. Decker BS, Goldfarb DS, Dargan PI, et al. Extracorporeal treatment for lithium poisoning: rystematic review and recommendations from the EXTRIP workgroup. CJASN. 2015; 10 (5): p.875-887. doi: 10.2215/​CJN.10021014 . | Open in Read by QxMD
  5. Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. International Journal of Bipolar Disorders. 2016; 4 (1). doi: 10.1186/s40345-016-0068-y . | Open in Read by QxMD
  6. Kosten TR, Forrest JN. Treatment of severe lithium-induced polyuria with amiloride.. Am J Psychiatry. 1986; 143 (12): p.1563-1568. doi: 10.1176/ajp.143.12.1563 . | Open in Read by QxMD
  7. Lithane. https://www.drugs.com/pro/lithane.html. Updated: June 1, 2006. Accessed: May 22, 2017.
  8. Lithium. https://www.drugs.com/ppa/lithium.html​​​​​​​. Updated: February 20, 2019. Accessed: May 10, 2019.
  9. Shireen A. Hedya; Akshay Avula; Henry D. Swoboda.. Lithium Toxicity. StatPearls. 2020 .